Dissecting the Single-Cell Transcriptome Network Underlying Gastric Premalignant Lesions and Early Gastric Cancer.
Peng Zhang, Mingran Yang, Yiding Zhang, Shuai Xiao, Xinxing Lai, Aidi Tan, Shiyu Du, Shao Li
Author Information
- Peng Zhang: MOE Key Laboratory of Bioinformatics, TCM-X Centre/Bioinformatics Division, BNRIST/Department of Automation, Tsinghua University, Beijing 10084, China.
- Mingran Yang: MOE Key Laboratory of Bioinformatics, TCM-X Centre/Bioinformatics Division, BNRIST/Department of Automation, Tsinghua University, Beijing 10084, China.
- Yiding Zhang: MOE Key Laboratory of Bioinformatics, TCM-X Centre/Bioinformatics Division, BNRIST/Department of Automation, Tsinghua University, Beijing 10084, China.
- Shuai Xiao: MOE Key Laboratory of Bioinformatics, TCM-X Centre/Bioinformatics Division, BNRIST/Department of Automation, Tsinghua University, Beijing 10084, China.
- Xinxing Lai: MOE Key Laboratory of Bioinformatics, TCM-X Centre/Bioinformatics Division, BNRIST/Department of Automation, Tsinghua University, Beijing 10084, China.
- Aidi Tan: MOE Key Laboratory of Bioinformatics, TCM-X Centre/Bioinformatics Division, BNRIST/Department of Automation, Tsinghua University, Beijing 10084, China.
- Shiyu Du: Department of Gastroenterology, China-Japan Friendship Hospital, Chaoyang District, Beijing 100029, China.
- Shao Li: MOE Key Laboratory of Bioinformatics, TCM-X Centre/Bioinformatics Division, BNRIST/Department of Automation, Tsinghua University, Beijing 10084, China. Electronic address: shaoli@tsinghua.edu.cn.
Intestinal-type gastric cancer is preceded by premalignant lesions, including chronic atrophic gastritis and intestinal metaplasia. In this study, we constructed a single-cell atlas for 32,332 high-quality cells from gastric antral mucosa biopsies of patients spanning a cascade of gastric premalignant lesions and early gastric cancer (EGC) using single-cell RNA sequencing. We then constructed a single-cell network underlying cellular and molecular characteristics of gastric epithelial cells across different lesions. We found that gland mucous cells tended to acquire an intestinal-like stem cell phenotype during metaplasia, and we identified OR51E1 as a marker for unique endocrine cells in the early-malignant lesion. We also found that HES6 might mark the pre-goblet cell cluster, potentially aiding identification of metaplasia at the early stage. Finally, we identified a panel of EGC-specific signatures, with clinical implications for the precise diagnosis of EGC. Our study offers unparalleled insights into the human gastric cellulome in premalignant and early-malignant lesions.
Basic Helix-Loop-Helix Transcription Factors
Cell Lineage
Enteroendocrine Cells
Epithelial Cells
Gastric Mucosa
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Goblet Cells
Humans
Precancerous Conditions
RNA, Neoplasm
Repressor Proteins
Single-Cell Analysis
Stomach Neoplasms
Transcription, Genetic
Transcriptome
Basic Helix-Loop-Helix Transcription Factors
HES6 protein, human
RNA, Neoplasm
Repressor Proteins
